Newborn skin maturity models for gestational age prediction

A multicenter clinical trial evaluated the accuracy of a novel device to detect preterm newborns. A portable multiband reflectance photometric device assessed 781 newborns’ skin maturity and used machine learning models to predict reference gestational age, adjusting it to birth weight and antenatal corticosteroid therapy exposure. The day difference between the reference and the test had a median of -1.4 (IQR: -2.1). Using established methods such as comparator ultrasound and last menstrual period (LMP), the medians were 0 (IQR: 4) and 0.01 (IQR: 4), respectively. For prematurity discrimination, the area under the receiver operating characteristic curve (AUROC) was 0.986 (95% CI: 0.977 to 0.994). In newborns with absent or unreliable LMP, the intent-to-discriminate analysis showed that the test generated correct classifications 95.8% of the time. The assessment of the newborn's skin maturity adjusted by learning models promises accurate pregnancy dating at birth without the use of antenatal ultrasound reference.

Newborn skin maturity models for gestational age prediction

A multicenter clinical trial evaluated the accuracy of a novel device to detect preterm newborns. A portable multiband reflectance photometric device assessed 781 newborns’ skin maturity and used machine learning models to predict reference gestational age, adjusting it to birth weight and antenatal corticosteroid therapy exposition. The day difference between the reference and the test had a median of -1.4 (IQR: -2.1). Using established methods such as comparator ultrasound and last menstrual period (LMP), the medians were 0 (IQR: 4) and 0.01 (IQR: 4), respectively. For prematurity discrimination, the area under the receiver operating characteristic curve (AUROC) was 0.986 (95% CI: 0.977 to 0.994). In newborns with absent or unreliable LMP, the intent-to-discriminate analysis showed that the test generated correct classifications 95.8% of the time. The assessment of the newborn's skin maturity adjusted by learning models promises accurate pregnancy dating at birth without the use of antenatal ultrasound reference.

Association between the chronology of gestation and the morphometrical skin characteristics at childbirth: a development of predictive model

ObjectiveThe structural maturation of the skin is considered a potential marker of pregnancy dating. This study investigated the correlation between the morphometrical skin characteristics with the pregnancy chronology to propose models for predicting gestational age.MethodsA cross-sectional analysis selected 35 corpses of newborns. The biopsy was performed up to 48 hours after death in the periumbilical abdomen, palm and sole regions. Pregnancy chronology was based on the obstetric ultrasound before 14 weeks. The dimensions of the skin layers, area of glands and connective fibrous tissue were measured with imaging software support. Univariate and multivariate regression models on morphometric values were used to predict gestational age.ResultsGestational age at birth ranged from 20.3 to 41.2 weeks. Seventy-one skin specimens resulted in the analysis of 1183 digital histological images. The correlation between skin thickness and gestational age was positive and strong in both regions of the body. The highest univariate correlation between gestational age and skin thickness was using the epidermal layer dimensions, in palm (r=0.867, p<0.001). The multivariate modelling with the thickness of the abdominal epidermis, the dermis and the area of the sebaceous glands adjusted had the highest correlation with gestational age (r=0.99, p<0.001).ConclusionThe thickness of the protective epidermal barrier is, in itself, a potential marker of pregnancy dating. However, sets of values obtained from skin morphometry enhanced the estimation of the gestational age. Such findings may support non-invasive image approaches to estimate pregnancy dating with various clinical applications.

Associations of circulating folate, vitamin B12 and homocysteine concentrations in early pregnancy and cord blood with epigenetic gestational age: the Generation R Study

Background Circulating folate, vitamin B12 and homocysteine concentrations during fetal development have been associated with health outcomes in childhood. Changes in fetal DNA methylation may be an underlying mechanism. This may be reflected in altered epigenetic aging of the fetus, as compared to chronological aging. The difference between gestational age derived in clinical practice and gestational age predicted from neonatal DNA methylation data is referred to as gestational age acceleration. Differences in circulating folate, vitamin B12 and homocysteine concentrations during fetal development may be associated with gestational age acceleration. Results Up to 1346 newborns participating in the Generation R Study, a population-based prospective cohort study, had both cord blood DNA methylation data available and information on plasma folate, serum total and active B12 and plasma homocysteine concentrations, measured in early pregnancy and/or in cord blood. A subgroup of 380 newborns had mothers with optimal pregnancy dating based on a regular menstrual cycle and a known date of last menstrual period. For comparison, gestational age acceleration was calculated based the method of both Bohlin and Knight. In the total study population, which was more similar to Bohlin’s training population, one standard deviation score (SDS) higher maternal plasma homocysteine concentrations was nominally associated with positive gestational age acceleration [0.07 weeks, 95% confidence interval (CI) 0.02, 0.13] by Bohlin’s method. In the subgroup with pregnancy dating based on last menstrual period, the method that was also used in Knight’s training population, one SDS higher cord serum total and active B12 concentrations were nominally associated with negative gestational age acceleration [(− 0.16 weeks, 95% CI − 0.30, − 0.02) and (− 0.15 weeks, 95% CI − 0.29, − 0.01), respectively] by Knight’s method. Conclusions We found some evidence to support associations of higher maternal plasma homocysteine concentrations with positive gestational age acceleration, suggesting faster epigenetic than clinical gestational aging. Cord serum vitamin B12 concentrations may be associated with negative gestational age acceleration, indicating slower epigenetic than clinical gestational aging. Future studies could examine whether altered fetal epigenetic aging underlies the associations of circulating homocysteine and vitamin B12 blood concentrations during fetal development with long-term health outcomes.

Premature or Small for Gestational Age Discrimination: International Multicenter Trial Protocol for Classification of the Low-Birth-Weight Newborn Through the Optical Properties of the Skin

Background A low birth weight is an independent risk factor for adverse infant outcomes and a predictor of chronic disease in adulthood. In these situations, differentiating between prematurity and small for gestational age (SGA) or simultaneous conditions is essential to ensuring adequate care. Such diagnoses, however, depend on reliable pregnancy dating, which can be challenging in developing countries. A new medical optoelectronic device was developed to estimate gestational age (GA) at birth based on newborn skin reflection. Objective This study will aim to evaluate the device’s ability to detect prematurity or SGA, or both conditions simultaneously as well as predict short-term pulmonary complications in a cohort of low-birth-weight newborns. Methods This study protocol was designed for a multicenter cohort including referral hospitals in Brazil and Mozambique. Newborns weighing 500-2500 g will be eligible for inclusion with the best GA available, considering the limited resources of low-income countries. Comparator-GA is based on reliable last menstrual period dating or ultrasound assessment before 24 weeks’ gestation. Estimated GA at birth (Test-GA) will be calculated by applying a novel optoelectronic device to the newborn’s skin over the sole. The average difference between Test-GA and Comparator-GA will be analyzed, as will the percentage of newborns who are correctly diagnosed as preterm or SGA. In addition, in a nested case–control study, the accuracy of skin reflection in the prediction of prematurity-related respiratory problems will be evaluated. The estimated required sample size is 298 newborns. Results Teams of health professionals were trained, and standard operating procedures were developed following the good practice guidelines for the clinical investigation of medical devices for human participants. The first recruitment started in March 2019 in Brazil. Data collection is planned to end in December 2020, and the results should be available in March 2021. Conclusions The results of this clinical study have the potential to validate a new device to easily assess postnatal GA, supporting SGA identification when pregnancy dating is unreliable or unknown. Trial Registration ReBec: RBR-33rnjf; http://www.ensaiosclinicos.gov.br/rg/RBR-33rnjf/ International Registered Report Identifier (IRRID) DERR1-10.2196/16477

Quality of Pregnancy Dating and Obstetric Interventions During Labor: Retrospective Database Analysis

Background The correct dating of pregnancy is critical to support timely decisions and provide obstetric care during birth. The early obstetric ultrasound assessment before 14 weeks is considered the best reference to assist in determining gestational age (GA), with an accuracy of ±5 to 7 days. However, this information is limited in many settings worldwide. Objective The aim of this study is to analyze the association between the obstetric interventions during childbirth and the quality of GA determination, according to the first antenatal ultrasound assessment, which assisted the calculation. Methods This is a hospital-based cohort study using medical record data of 2113 births at a perinatal referral center. The database was separated into groups and subgroups of analyses based on the reference used by obstetricians to obtain GA at birth. Maternal and neonatal characteristics, mode of delivery, oxytocin augmentation, and forceps delivery were compared between groups of pregnancies with GA determination at different reference points: obstetric ultrasound assessment 14 weeks, 20 weeks, and ≥20 weeks or without antenatal ultrasound (suboptimal dating). Ultrasound-based GA information was associated with outcomes between the interest groups using chi-square tests, odds ratios (OR) with 95% CI, or the Mann-Whitney statistical analysis. Results The chance of nonspontaneous delivery was higher in pregnancies with 14 weeks ultrasound-based GA (OR 1.64, 95% CI 1.35-1.98) and 20 weeks ultrasound-based GA (OR 1.58, 95% CI 1.31-1.90) when compared to the pregnancies with ≥20 weeks ultrasound-based GA or without any antenatal ultrasound. The use of oxytocin for labor augmentation was higher for 14 weeks and 20 weeks ultrasound-based GA, OR 1.41 (95% CI 1.09-1.82) and OR 1.34 (95% CI 1.04-1.72), respectively, when compared to those suboptimally dated. Moreover, maternal blood transfusion after birth was more frequent in births with suboptimal ultrasound-based GA determination (20/657, 3.04%) than in the other groups (14 weeks ultrasound-based GA: 17/1163, 1.46%, P=.02; 20 weeks ultrasound-based GA: 25/1456, 1.71%, P=.048). Cesarean section rates between the suboptimal dating group (244/657, 37.13%) and the other groups (14 weeks: 475/1163, 40.84%, P=.12; 20 weeks: 584/1456, 40.10%, P=.20) were similar. In addition, forceps delivery rates between the suboptimal dating group (17/657, 2.6%) and the other groups (14 weeks: 42/1163, 3.61%, P=.24; 20 weeks: 46/1456, 3.16%, P=.47) were similar. Neonatal intensive care unit admission was more frequent in newborns with suboptimal dating (103/570, 18.07%) when compared with the other groups (14 weeks: 133/1004, 13.25%, P=.01; 20 weeks: 168/1263, 13.30%, P=.01), excluding stillbirths and major fetal malformations. Conclusions The present analysis highlighted relevant points of health care to improve obstetric assistance, confirming the importance of early access to technologies for pregnancy dating as an essential component of quality antenatal care.

Premature or Small for Gestational Age Discrimination: International Multicenter Trial Protocol for Classification of the Low-Birth-Weight Newborn Through the Optical Properties of the Skin (Preprint)

BACKGROUND A low birth weight is an independent risk factor for adverse infant outcomes and a predictor of chronic disease in adulthood. In these situations, differentiating between prematurity and small for gestational age (SGA) or simultaneous conditions is essential to ensuring adequate care. Such diagnoses, however, depend on reliable pregnancy dating, which can be challenging in developing countries. A new medical optoelectronic device was developed to estimate gestational age (GA) at birth based on newborn skin reflection. OBJECTIVE This study will aim to evaluate the device’s ability to detect prematurity or SGA, or both conditions simultaneously as well as predict short-term pulmonary complications in a cohort of low-birth-weight newborns. METHODS This study protocol was designed for a multicenter cohort including referral hospitals in Brazil and Mozambique. Newborns weighing 500-2500 g will be eligible for inclusion with the best GA available, considering the limited resources of low-income countries. Comparator-GA is based on reliable last menstrual period dating or ultrasound assessment before 24 weeks’ gestation. Estimated GA at birth (Test-GA) will be calculated by applying a novel optoelectronic device to the newborn’s skin over the sole. The average difference between Test-GA and Comparator-GA will be analyzed, as will the percentage of newborns who are correctly diagnosed as preterm or SGA. In addition, in a nested case–control study, the accuracy of skin reflection in the prediction of prematurity-related respiratory problems will be evaluated. The estimated required sample size is 298 newborns. RESULTS Teams of health professionals were trained, and standard operating procedures were developed following the good practice guidelines for the clinical investigation of medical devices for human participants. The first recruitment started in March 2019 in Brazil. Data collection is planned to end in December 2020, and the results should be available in March 2021. CONCLUSIONS The results of this clinical study have the potential to validate a new device to easily assess postnatal GA, supporting SGA identification when pregnancy dating is unreliable or unknown. CLINICALTRIAL ReBec: RBR-33rnjf; http://www.ensaiosclinicos.gov.br/rg/RBR-33rnjf/ INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16477